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THEJOURNALOFBIOLOGICALCHEMISTRYVol.280,No.24,IssueofJune17,pp.22741–22748,2005
©2005byTheAmericanSocietyforBiochemistryandMolecularBiology,Inc.PrintedinU.S.A.
CriticalAssessmentofImportantRegionsintheSubunit
AssociationandCatalyticActionoftheSevereAcute
RespiratorySyndromeCoronavirusMainProtease*
Receivedforpublication,March8,2005,andinrevisedform,April4,2005
Published,JBCPapersinPress,April14,2005,DOI10.1074/jbc.M502556200
Wen-ChiHsu,Hui-ChuanChang,Chi-YuanChou,Pui-JenTsai,Pei-InLin,andGu-GangChang‡
FromtheFacultyofLifeSciences,InstituteofBiochemistry,andStructuralBiologyProgram,
NationalYang-MingUniversity,Taipei112,Taiwan
Thesevereacuterespiratorysyndrome(SARS)coro-length,andtheorganizationissimilartothatofothercorona-
navirus(CoV)mainproteaserepresentsanattractiveviruses.Thereplicasegeneencodestwooverlappingpolypro-
targetforthedevelopmentofnovelanti-SARSagents.teins,polyprotein1a(450kDa)andpolyprotein1ab(750
ThetertiarystructureoftheproteaseconsistsoftwokDa).Thepolyproteinsarecleavedbytheinternallyencoded
distinctfolds.OneistheN-terminalchymotrypsin-likemainprotease(Mpro,3CL),whichisrequiredfortheproduction
foldthatconsistsoftwostructuraldomainsandconsti-ofnewinfectiousviruses.Themainproteaserepresentsan
tutesthecatalyticmachinery;theotheristhe
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